Target Information

Target General Infomation
Target ID
T38179
Former ID
TTDS00228
Target Name
Beta-lactamase
Gene Name
blaZ
Synonyms
Cephalosporinase; blaZ
Target Type
Successful
Disease Bacterial infections [ICD9: 001-009, 010-018, 020-027, 030-041, 080-088, 090-099, 100-104; ICD10: A00-B99]
Gram-positive bacterial infection [ICD9: 001-009, 010-018, 020-027, 030-041, 080-088, 090-099, 100-104]
Infections [ICD9: 001-139; ICD10: A00-B99]
Multidrug resistant infection [ICD10: A00-B99]
Methicillin-resistant staphylococcus aureus infection [ICD10: B95.62]
Otitis media [ICD10: H65-H67]
Streptococcus pneumoniae infection [ICD10: J13]
Serious infections [ICD9: 001-139; ICD10: A00-B99]
Toxicity [ICD10: T36-T50, T51-T65]
Unspecified [ICD code not available]
Function
This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
BioChemical Class
Carbon-nitrogen hydrolase
Target Validation
T38179
UniProt ID
P00807
EC Number
EC 3.5.2.6
Sequence
MKKLIFLIVIALVLSACNSNSSHAKELNDLEKKYNAHIGVYALDTKSGKEVKFNSDKRFA
YASTSKAINSAILLEQVPYNKLNKKVHINKDDIVAYSPILEKYVGKDITLKALIEASMTY
SDNTANNKIIKEIGGIKKVKQRLKELGDKVTNPVRYEIELNYYSPKSKKDTSTPAAFGKT
LNKLIANGKLSKENKKFLLDLMLNNKSGDTLIKDGVPKDYKVADKSGQAITYASRNDVAF
VYPKGQSEPIVLVIFTNKDNKSDKPNDKLISETAKSVMKEF
Drugs and Mode of Action
Drug(s) Ceftolozane/tazobactam Drug Info Approved Unspecified [1]
Clavulanate Drug Info Approved Bacterial infections [2]
Tazobactam Drug Info Approved Bacterial infections [3]
CAZ AVI Drug Info Phase 3 Serious infections [4]
CXL Drug Info Phase 2 Methicillin-resistant staphylococcus aureus infection [5]
MK-7655 Drug Info Phase 2 Bacterial infections [6]
ME-1071 Drug Info Phase 1 Bacterial infections [7]
RASV-Sp Drug Info Phase 1 Streptococcus pneumoniae infection [8]
2085-P Drug Info Discontinued in Phase 3 Otitis media [9]
DA-7101 Drug Info Discontinued in Phase 3 Gram-positive bacterial infection [10]
P1A Drug Info Discontinued in Phase 2 Toxicity [11]
BRL-42715 Drug Info Terminated Bacterial infections [12]
CL-186659 Drug Info Terminated Bacterial infections [13]
Ro-48-1220 Drug Info Terminated Bacterial infections [14]
Ro-48-5545 Drug Info Terminated Bacterial infections [15]
Ro-48-8724 Drug Info Terminated Multidrug resistant infection [16]
SB-236049 Drug Info Terminated Bacterial infections [17]
Inhibitor (P-Iodophenylacetylamino)Methylphosphinic Acid Drug Info [18]
1-Aminopropane-1,2,3-tricarboxylic acid Drug Info [19]
2-(N-Morpholino)-Ethanesulfonic Acid Drug Info [18]
2-(Sulfanylmethyl)phenylphosphonic acid Drug Info [20]
2-mercaptophenylphosphonic acid Drug Info [20]
2-Methyl-2,4-Pentanediol Drug Info [18]
2-phenyl-1H-imidazole-4-carboxylic acid Drug Info [21]
3-Amino-3-(methoxycarbonyl)-1,5-pentandioic acid Drug Info [19]
3-ethoxycarbonylpyroglutamate Drug Info [19]
3-Nitrophenylboronic Acid Drug Info [18]
4,4'-Biphenyldiboronic Acid Drug Info [18]
4-(Carboxyvin-2-Yl)Phenylboronic Acid Drug Info [18]
4-Carboxyphenylboronic Acid Drug Info [18]
4-iodo-acetamido phenylboronic acid Drug Info [18]
4-Methyl-3-(2-oxo-azetidin-1-yl)-benzoic acid Drug Info [22]
4-[(METHYLSULFONYL)AMINO]BENZOIC ACID Drug Info [21]
5-Fluoro-2-sulfanyl-phenylphosphonic acid Drug Info [20]
5-hydroxymethylbenzo[b]thiophen-2-ylboronic acid Drug Info [23]
5-methyl-benzo[b]thiophen-2-ylboronic acid Drug Info [23]
Acetate Ion Drug Info [18]
Acylated Ceftazidime Drug Info [18]
Alpha-Sulfanyl(2,4-dichlorobenzyl)phosphonic acid Drug Info [20]
Alpha-Sulfanyl(2-methoxybenzyl)phosphonic acid Drug Info [20]
Alpha-Sulfanyl(4-bromobenzyl)phosphonic acid Drug Info [20]
Alpha-Sulfanyl(4-chlorobenzyl)phosphonic acid Drug Info [20]
Alpha-Sulfanyl(4-fluorobenzyl)phosphonic acid Drug Info [20]
Alpha-Sulfanylbenzylphosphonic acid Drug Info [20]
Alpha-Sulfanylpropylphosphonic acid Drug Info [20]
Benzo[b]thiophen-2-ylboronic acid Drug Info [23]
Benzo[B]Thiophene-2-Boronic Acid Drug Info [18]
BRL-42715 Drug Info [24]
Carbamic Acid Drug Info [18]
Clavulanate Drug Info [25]
Clavulanate+Amoxicillin Drug Info [26]
DA-7101 Drug Info [10]
Degraded Cephaloridine Drug Info [18]
Diisopropyl 1-mercaptopropylphosphonate Drug Info [20]
Diisopropyl 2-(sulfanylmethyl)phenylphosphonate Drug Info [20]
Diisopropyl mercapto(phenyl)methylphosphonate Drug Info [20]
Hydrolyzed Cephalothin Drug Info [18]
M-Aminophenylboronic Acid Drug Info [18]
ME-1071 Drug Info [27]
MK-7655 Drug Info [28]
N-2-Thiophen-2-Yl-Acetamide Boronic Acid Drug Info [18]
PCNOTAXIME GROUP Drug Info [21]
Ro-48-5545 Drug Info [29]
SB-236049 Drug Info [17]
Sucrose Drug Info [30]
Tazobactam Drug Info [31]
Thiophene-2-ylboronic acid Drug Info [23]
Tribenzyl 2-aminopropane-1,2,3-tricarboxylate Drug Info [19]
Triethyl 2-aminopropane-1,2,3-tricarboxylate Drug Info [19]
[[N-(Benzyloxycarbonyl)Amino]Methyl]Phosphate Drug Info [18]
Modulator 2085-P Drug Info [32]
CAZ AVI Drug Info [33]
Ceftolozane/tazobactam Drug Info [34]
CL-186659 Drug Info [32]
CXL Drug Info [35]
P1A Drug Info [36]
Ro-48-1220 Drug Info [37]
Ro-48-8724 Drug Info [38]
References
REF 1Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 2FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 065063.
REF 3Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 4ClinicalTrials.gov (NCT01644643) Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens. U.S. National Institutes of Health.
REF 5Clinical pipeline report, company report or official report of AstraZeneca.
REF 6Clinical pipeline report, company report or official report of Merck (May 7, 2015).
REF 7Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027139)
REF 8Rapid, Sensitive Recovery of Recombinant Attenuated Salmonella enterica Serovar Typhi Vaccine Strains from Human Blood. Clin Vaccine Immunol. 2013 September; 20(9): 1473-1478.
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001248)
REF 10Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
REF 11Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020134)
REF 12Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001128)
REF 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004648)
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004684)
REF 15Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008139)
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008187)
REF 17Identification of a series of tricyclic natural products as potent broad-spectrum inhibitors of metallo-beta-lactamases. Antimicrob Agents Chemother. 2002 Jun;46(6):1880-6.
REF 18How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 19Bioorg Med Chem Lett. 2009 Jul 1;19(13):3593-7. Epub 2009 May 6.Discovery of novel lipophilic inhibitors of OXA-10 enzyme (class D beta-lactamase) by screening amino analogs and homologs of citrate and isocitrate.
REF 20J Med Chem. 2010 Jul 8;53(13):4862-76.Mercaptophosphonate compounds as broad-spectrum inhibitors of the metallo-beta-lactamases.
REF 21The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 22J Med Chem. 1988 Feb;31(2):370-4.N-aryl 3-halogenated azetidin-2-ones and benzocarbacephems, inhibitors of beta-lactamases.
REF 23J Med Chem. 2007 Nov 15;50(23):5644-54. Epub 2007 Oct 23.Optimizing cell permeation of an antibiotic resistance inhibitor for improved efficacy.
REF 24In vitro evaluation of BRL 42715, a novel beta-lactamase inhibitor. Antimicrob Agents Chemother. 1989 Sep;33(9):1580-7.
REF 25A sensitive coupled HPLC/electrospray mass spectrometry assay for SPM-1 metallo-beta-lactamase inhibitors. Assay Drug Dev Technol. 2009 Apr;7(2):170-9.
REF 26Emerging therapies for the treatment and prevention of otitis media. Expert Opin Emerg Drugs. 2006 May;11(2):251-64.
REF 27Multidrug-resistant Gram-negative bacterial infections: are you ready for the challenge. Curr Clin Pharmacol. 2014 Feb;9(1):27-38.
REF 28Discovery of MK-7655, a beta-lactamase inhibitor for combination with Primaxin?. Bioorg Med Chem Lett. 2014 Feb 1;24(3):780-5.
REF 29Potentiation of beta-lactams against Pseudomonas aeruginosa strains by Ro 48-1256, a bridged monobactam inhibitor of AmpC beta-lactamases. J Antimicrob Chemother. 1997 Sep;40(3):335-43.
REF 30Ten S, Maclaren N: Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004 Jun;89(6):2526-39.
REF 31Selection of TNF-alpha binding affibody molecules using a beta-lactamase protein fragment complementation assay. N Biotechnol. 2009 Jul 1.
REF 32US patent application no. 2004,0023,290, Novel therapeutic agents that modulate enzymatic processes.
REF 33NXL104 irreversibly inhibits the beta-lactamase from Mycobacterium tuberculosis. Biochemistry. 2012 Jun 5;51(22):4551-7. Epub 2012 May 22.
REF 342014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
REF 35Beta-Lactam Antibiotics Renaissance. Antibiotics. 2014, 3(2), 193-215.
REF 36IPSAT P1A, a class A beta-lactamase therapy for the prevention of penicillin-induced disruption to the intestinal microflora. Curr Opin Investig Drugs. 2009 Aug;10(8):838-44.
REF 37Comparative in vitro activity of apalcillin alone and combined with Ro 48-1220, a novel penam beta-lactamase inhibitor. Clin Microbiol Infect. 1995 Feb;1(2):86-100.
REF 38Activity of a broad-spectrum cephalosporin (Ro 48-8391) alone and in combination with two novel beta-lactamase inhibitors (Ro 48-5545 and Ro 48-8724). Diagn Microbiol Infect Dis. 1998 Oct;32(2):85-94.

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